Development of Patient Decision Aids for Plaque Psoriasis and Acne.

INTRODUCTION: Despite proven benefits in other medical specialties, there is a paucity of patient decision aids (PDAs) in dermatology. The present study developed online PDAs for acne and psoriasis, incorporating iterative patient and physician feedback, in accordance with International Patient Decision Aid Standards (IPDAS). DESIGN AND METHOD: Content was adapted from clinical practice guidelines and primary research and formatted for an 8th grade reading level. Feedback on content and format was obtained through focus groups with 15 psoriasis patients and survey with 34 acne patients. Feedback on presentation and clinical utility of the PDAs was gathered by survey from 51 physicians in Canada and the United States. Each data collection stage informed further development. RESULTS: Demand for decision support, and satisfaction with the PDAs was high among patients. Physicians were approving of content and expressed a strong interest in PDA use. CONCLUSION: Patients and physicians approve of the PDAs' content, format, and intended use. Online PDAs allow accessibility for patients and may reduce barriers to use for physicians.

Individual and combined effects of acute and chronic running loads on injury risk in elite Australian footballers.

A model that takes into account the current workload, and the workload the athlete has been prepared for, as an acute:chronic workload ratio has been previously used as a novel way to monitor training load and injury risk. Fifty-nine elite Australian football players from one club participated in this 2-year study. Global Positioning System technology was used to provide information on running workloads of players. An injury was defined as any non-contact "time-loss" injury. One-week (acute), along with 4-week (chronic) workloads were calculated for a range of variables. The size of the acute workload in relation to the chronic workload was calculated as an acute:chronic workload ratio. An acute:chronic workload ratio of >2.0 for total distance during the in-season was associated with a 5 to 8-fold greater injury risk in the current [relative risk (RR) = 8.65, P = 0.001] and subsequent week (RR = 5.49, P = 0.016). Players with a high-speed distance acute:chronic workload ratio of >2.0 were 5-11 times more likely to sustain an injury in the current (RR = 11.62, P = 0.006) and subsequent week (RR = 5.10, P = 0.014). These findings demonstrate that sharp increases in running workload increase the likelihood of injury in both the week the workload is performed, and the subsequent week.

Comparison of capillary and venous blood in the analysis of concentration and function of leucocyte sub-populations.

PURPOSE: Compare capillary and venous blood in the analysis of concentration and function of leucocyte sub-populations. This study hypothesised that capillary samples may be used in a site-specific manner as an alternative source of blood samples for assays of leucocyte concentration and neutrophilic phagocytic function and reactive oxygen species (ROS) production, allowing acquisition of multiple samples to better monitor transient but significant post-exercise immune modulation. METHODS: Resting blood samples were simultaneously obtained from vein, finger and earlobe of healthy subjects (n = 10, age: 25.1 ± 3.1 years). Leucocyte concentrations were measured using a five-part differential haematological analyser. Leucocyte sub-populations (CD3, CD4, CD8, CD19, CD56, CD14) and granulocytic functional-related (CD11b, CD18, CD16b, CD66b) surface antigen markers, neutrophil phagocytosis (FITC-labelled Escherichia coli) and stimulated ROS production (DHR) were quantified utilizing flow cytometry. A MANOVA (α < 0.05 significance) analysed the effects of the different sampling sites in the concentrations of leucocyte populations, their surface antigen expression and granulocytic functions. RESULTS: Leucocyte concentration and neutrophilic ROS production yielded non-significant differences between sampling sites. Expression of granulocytic surface antigens was increased in both capillary sites compared to venous site (p = 0.008), particularly for adhesion markers CD11b/CD18. The percentage of neutrophils performing phagocytosis was higher in venous samples compared to finger (p = 0.025). Increased number of E. coli ingested was observed in venous sample compared to finger (p = 0.001) and to earlobe (p = 0.006). CONCLUSION: Whilst attention must be paid for varying neutrophilic surface antigen expression and further studies are needed to establish appropriate reference ranges, this study supports the use of capillary blood samples in a site-specific manner to enhance sampling capabilities field-based research.

A comparison of upper and lower body energetics during high-intensity exercise.

AIM: The aim of the present study was to measure and compare the aerobic, anaerobic alactic and anaerobic lactic energy system contribution during the 30-sec Wingate anaerobic test (WAnT) for the upper and lower body within the same individuals. METHODS: Physically active men (N.=14) completed two WAnTs on an electronic arm ergometer and a cycle ergometer separated by three days. A fly wheel braking force corresponding to 5% and 7.5% of the participants body weight was used for the upper and lower body WAnTs respectively. Oxygen uptake and blood lactate were measured before, during and after both WAnTs, and body composition was measured using dual-energy X-ray absorptiometry (DEXA). RESULTS: The anaerobic lactic energy system contribution was significantly (P<0.01) higher during the upper body (60.3±5.6%) compared to the lower body (46.9±6.9%) WAnT. The contribution of the anaerobic alactic system was significantly higher (P<0.01) during the lower body (36.5±6.3%) compared to the upper body (28.3±4.9%) WAnT, with the aerobic system contribution significantly (P<0.05) higher for the lower body (16.8±2.5%) compared to the upper body (11.4±1.4%) WAnT. CONCLUSION: The anaerobic lactic energy system provides over 60% of the energy requirements during an upper body WAnT but provides less the 50% during the lower body WAnT. In contrast, the aerobic and anaerobic alactic energy system contribution was significantly less for the upper body WAnT compared to the lower body WAnT.

Changes in sleep quantity and efficiency in professional rugby union players during home based training and match-play.

Adequate sleep is paramount to athlete recovery and performance, however little is know about the typical sleep patterns of professional rugby union players during home based training and match-play in the competitive season. AIM: The aim of the present study was to monitor changes in sleep quantity and efficiency of elite male rugby union players over a twelve night period, which included training and two competitive matches. METHODS: A total of ten elite male rugby union players from a selected team, participated in the study. Athletes sleep quantity and efficiency was monitored over a twelve night period using the Bodymedia sensewear units (BSU). RESULTS: There was a significant difference in sleep quantity (p<0.05) on game nights compared to non game night, with players sleeping less on game nights. Time to sleep on game nights was also significantly (p<0.05) later than non game nights. There was no significant difference in sleep efficiency or time at wake over the twelve night period. Sleep efficiency is defined as a percentage score calculated by incorporating movement and physiological measures over the sleep duration as determined by the BSU. Also there was no significant difference between sleep parameters on the game nights. The findings show players have significantly (p<0.05) reduced sleep following a home game, which is of concern considering the established negative influence of sleep deprivation on cognitive and physical performance. CONCLUSION: This data may assist coaching, medical and performance staff to develop and implement team and individualised sleep monitoring regimes to optimise training and on-field performance.

Upper and lower body anaerobic performance of semi-elite Rugby League players.

AIM: The aim of this study was to measure the upper and lower body anaerobic performance of semi-elite Rugby League (RL) players. METHODS: Twenty-two semi-professional RL players and 24 physically active but untrained men completed two Wingate anaerobic tests (WAnT) on an electronic arm ergometer and a cycle ergometer separated by three days. Percent body fat was used determined from the sum of six skinfolds and upper and lower muscle cross-sectional area (CSA) was calculated from anthropometric data. RESULTS: Upper and lower body absolute peak (P=0.035, P=0.002) and mean (P=0.005, P=0.031) power were higher in the RL group compared to the control group. Upper and lower body relative peak power was higher (P=0.022, P=0.047) in the control group compared to the RL group. Peak and mean power (relative and absolute) were higher (P≤0.05) in the lower body compared to the upper body. Peak and mean power relative to upper and lower muscle CSA was higher (P≤0.001) in the upper body compared to the lower body for both groups. CONCLUSION: Semi-elite Rugby League players have well developed absolute anaerobic power, but relative to body weight upper and lower body anaerobic power is not well developed. The upper body is able to generate more power relative to body weight and muscle CSA compared to the lower body during the WAnT. Future studies should examine the upper body anaerobic performance of elite RL players and other sports that have similar upper body demands.

Emergency Do Not Consume/do Not Use concentrations for potassium permanganate in drinking water.

Over the past decade, regulatory authorities and water purveyors have become increasingly concerned with accidental or intentional adulteration of municipal drinking water. Emergency response guidelines, such as the 'Do Not Consume' or use concentration limits derived herein, can be used to notify the public in such cases. Potassium permanganate (KMnO(4)) is used to control iron concentrations and to reduce the levels of nuisance materials that affect odor or taste of finished drinking water. Manganese (Mn) is recognized an essential nutrient, permanganate (MnO4 (-)) and manganous (Mn(+2)) ions are caustic, and the acute toxicity of KMnO(4) is defined by its oxidant/irritant properties and by the toxicity of Mn. Ingestion of small amounts (4-20 mg/kg) of aqueous KMnO(4) solutions that are above 200 mg/L causes gastrointestinal distress, while bolus ingestion has caused respiratory arrest following coagulative necrosis and hemorrhage in the esophagus, stomach, or liver. Dilute KMnO(4) solutions (1-100 mg/L) are used as a topical antiseptics and astringents, but >1:5000 (200 mg/L) dilutions can irritate or discolor sensitive mucous membranes and direct skin or ocular contact with concentrated KMnO(4) can perforate tissues. Based on clinical experience with 200 mg/L KMnO(4), a Do Not Consume concentration of 7 mg/L KMnO(4) (equivalent to 2 mg Mn/L) is recommended. Recognizing limited empirical data from which to calculate an ocular reference value, a skin contact 'Do Not Use' concentration of 30 mg Mn/L is recommended based on the skin irritation in some patients after a 10-min contact with 100 mg KMnO4/L.

Does upper body strength and power influence upper body Wingate performance in men and women?

The aim of this study was to determine the influence of muscular strength and power on upper body Wingate performance in men and women. Muscular strength (1 repetition maximum bench press), muscular power (bench throws) and upper body anaerobic performance (Wingate Anaerobic Test (WAnT)) was assessed in 24 men and 16 women. Men had significantly ( P<0.001) higher absolute and relative peak and mean power and blood lactate concentration during the WAnT compared to their female counterparts. Men also produced significantly ( P<0.001) higher strength and absolute and relative peak and mean power during the bench press and throw, respectively, compared to the female participants. For men body mass and mean power produced during the bench throw explained approximately 84% and 87% of the variance in Wingate peak ( P<0.001 and P=0.039, respectively) and mean ( P<0.001 and P=0.028, respectively) power. For women mean power produced during the bench throw explained approximately 72% and 52% of the variance in Wingate peak ( P=0.002) and mean ( P=0.017) power, respectively. For men body mass and to a lesser extent muscular power best predicts upper body Wingate performance while for women only muscular power predicts upper body Wingate performance.

Aspects of nonlinear dielectric spectroscopy of biological cell suspensions.

In this paper the technique of nonlinear dielectric spectroscopy is employed to examine the nonlinear response of a suspension of the yeast S. cerevisiae to a low frequency perturbating ac electric field. Metabolically active and resting yeast states, as well as the electrolyte medium are considered, and experimental time-course spectral data are presented. Conductivity is found to increase in the active case, resulting in variations in magnitude of the applied field. An empirical model is fitted to the experimental data at discrete points over time, enabling simulation and resulting in a software-based method to compensate for these variations in effective field strength.

Spatial glutathione and cysteine distribution and chemical modulation in the early organogenesis-stage rat conceptus in utero.

Glutathione (GSH), cysteine, and other low-molecular-weight thiols (LMWT) play a vital role in the detoxication of xenobiotics and endogenous chemicals. Differential alterations of LMWT status in various cell types of the developing embryo may underlie cell-specific sensitivity or resistance to xenobiotics and contribute to embryotoxicity. This study describes the spatial and temporal distribution of LMWTs in rat conceptuses and alterations produced by the non-teratogenic GSH modulator, acetaminophen (APAP). Pregnant female rats were given 125, 250, or 500 mg/kg APAP (po) on gestational day 9. Conceptal LMWT was localized histochemically using mercury orange in cryosections, and GSH and cysteine concentrations were measured by HPLC analysis. Mercury orange histofluorescence revealed a non-uniform distribution of LMWT in untreated conceptal tissues, with strongest staining observed in the ectoplacental cone (EPC), visceral yolk sac (VYS), and embryonic heart. Less intense staining was observed in the neuroepithelium. Following treatment with APAP, tissue-associated LMWT decreased dramatically except in the EPC, while exocoelomic fluid LMWT, and LMWT within embryonic lumens, increased. Exposure to 250 mg/kg APAP decreased embryonic GSH after 6 and 24 h by 46% and 38%, respectively. Acetaminophen (500 mg/kg) decreased embryonic and VYS cysteine content by 54% and 83%, respectively, after 24 h. Acetaminophen alters the spatial distribution of LMWT in rat conceptuses, particularly with respect to cysteine. The mobilization of cysteine following chemical insult may influence the ability of conceptal cells to maintain normal GSH status due to reduced availability of cysteine for de novo GSH synthesis.

Risk of mother-to-infant transmission of HIV-1 is not reduced in CCR5/delta32ccr5 heterozygotes.

To determine if the 32-bp deletion of the chemokine receptor CCR5 (delta32ccr5) protects against mother-to-infant transmission of HIV-1, specimens from all uninfected and infected children who were perinatally exposed to HIV-1 and observed since 1988 and whose mothers did not take zidovudine were assessed for delta32ccr5. The CCR5 genotype was determined using polymerase chain reaction (PCR) for 122 subjects, of whom 73 were HIV-1 infected and 49 were perinatally exposed but uninfected; 70% and 71%, respectively, were Caucasian. Eleven of 73 (15%) infected children and 4 of 49 (8%) exposed uninfected children were CCR5/delta32ccr5 heterozygotes (p = 0.40). Among subjects who had at least one Caucasian parent or grandparent, 11 of 51 (22%) HIV-1-infected persons and 4 of 35 (11%) uninfected persons were heterozygotes. None were homozygous for the delta32ccr5 allele. The estimated relative risk for mother-to-infant HIV-1 transmission in heterozygotes was 2.0. Furthermore, the 95% confidence interval (0.6, 7.3) suggested that it is unlikely that the true relative risk was <0.6. Thus, the infant CCR5/delta32ccr5 heterozygous genotype was not associated with a diminished risk of perinatally acquired HIV-1 infection.

Analysis of the maternal components of the AIDS clinical trial group 076 zidovudine regimen in the prevention of mother-to-infant transmission of human immunodeficiency virus type 1.

To gain insight into the protective effects of the three components of the zidovudine regimen used in AIDS Clinical Trial Group (ACTG) 076 on mother-to-infant transmission of human immunodeficiency virus (HIV) type 1, 188 zidovudine-treated women and their untreated infants from five HIV-1 obstetric centers were retrospectively studied. The overall rate of mother-to-infant transmission was 12.3% (95% confidence interval [CI], 7.9%-18.0%). When the 38 women with <200 CD4 cells/microL were excluded, the mother-to-infant transmission rate was 8.8% (95% CI, 4.6%-14.8%). This rate compares favorably with the 8.3% transmission in the zidovudine arm of the ACTG 076 study. Apart from low (<200/microL) maternal CD4 cells (P = .016), no factors, including the duration of zidovudine therapy during gestation and intravenous administration of zidovudine during labor, affected the rate of mother-to-infant transmission. These findings suggest that antenatal oral zidovudine may be as effective as antenatal oral plus intravenous zidovudine during labor and the three-component ACTG 076 regimen in decreasing mother-to-infant HIV-1 transmission.

Effect of pregnancy and zidovudine therapy on viral load in HIV-1-infected women.

The objective of this study was to determine the effect of pregnancy and zidovudine (ZDV) on viral load in HIV-1 infected women. A prospective nonrandomized cohort study was conducted at a university medical center and affiliated clinic and included 44 HIV-1-seropositive pregnant women seen between June 1991 and September 1995. Twenty-three women initiated ZDV therapy during their pregnancy. Seventeen women did not take antiretrovirals, and four women took ZDV prior to and throughout pregnancy. HIV-1 viral load as determined by quantitative peripheral blood mononuclear cell (PBMC) culture and quantitative plasma RNA levels was measured at various times during pregnancy and in the postpartum period. HIV-1 load, by both infectivity and RNA levels, was relatively low and remained stable during pregnancy and through 6 weeks post partum. Initiation of ZDV therapy during pregnancy did not result in a significant decrease in viral load at delivery when controlling for the effect of pregnancy. In those women who received ZDV therapy only during pregnancy, there was a trend toward an increase in viral load measured by PBMC infectivity 6 months post partum compared with the levels before the initiation of ZDV. Mother-to-child transmission of HIV-1 occurred in one of 27 (4%) ZDV-treated women and in two of 16 (12.5%) untreated women. Among HIV-1-infected pregnant women with low viral levels, HIV-1 plasma RNA and infectivity remained stable during and after gestation. Although these results are based on a relatively small number of women and should be considered preliminary, the lack of significant ZDV-associated diminution in viral levels suggests that the protective effect of ZDV on the mother-to-child transmission of HIV-1 may not be due to the reduction in maternal viral levels but, by inference, may be due to the prevention of HIV-1 reverse transcription in the newborn.

Specific labeling of isoprenylated proteins: application to study inhibitors of the post-translational farnesylation and geranylgeranylation.

Specific labeling of either farnesylated or geranylgeranylated proteins in human PC-3 prostate cancer cell line was obtained by suppression of mevalonic acid biosynthesis with lovastatin, 50 microM, followed by supplementation of cell culture medium with either [3H]farnesyl- or [3H]geranylgeranyl-pyrophosphate. The immunoprecipitation of either a farnesylated (p21 ras) or geranylgeranylated (p21 rap 1) protein demonstrated that labeling was specific since proteins were detected only if the appropriate isoprenoid was added to the culture medium. TLC analysis indicated that no conversion of one isoprenoid to the other occurred in these conditions. The selective labeling of either farnesylated or geranylgeranylated proteins may be a valuable tool for the development of inhibitors of isoprenoid transferases as a potential new class of antitumor agents.

6-[18F]fluoro-L-dopa and cerebral blood flow in unilaterally MPTP-treated monkeys.

Intravenous administration of 15O-labeled water and 6-[18F]-L-fluorodopa were used to assess abnormal striatal activity in monkeys after long-term recovery of unilateral lesions of the dopaminergic nigro-striatal system induced by the neurotoxin MPTP. PET data were examined in relation to behavioral and biological parameters. Cerebral blood flow and 6-[18F]-L-DOPA uptake were found to be significantly reduced in the lesioned striatum, compared to the unaffected side and to normal controls. There was no correlation between cerebral blood flow and any of the behavioral parameters. The uptake rate constant of 18F-DOPA from blood to striatum and the ratios of striatum to occipital areas were highly correlated to the concentrations of homovanillic acid in the cerebrospinal fluid of the same animals but not to the rotational behavior. This MPTP-induced model of striatal dopamine deficiency in primates presents similarities with idiopathic Parkinson's disease and may be used to evaluate the effects of dopaminergic lesions and transplants on brain function.

Suramin rapidly alters cellular tyrosine phosphorylation in prostate cancer cell lines.

Suramin, a synthetic polysulfonated anionic compound, is known to abrogate the activity of a variety of growth factors that serve as ligands for receptor-class protein-tyrosine kinases. Based on this information, we initially hypothesized that suramin treatment would be associated with decreased tyrosine phosphorylation. Upon testing this hypothesis in prostate cancer cell lines, we found that the most conspicuous effect of suramin was to increase the tyrosine phosphorylation of several distinct proteins. Further analyses indicate that suramin-induced increases in tyrosine phosphorylation represent a generalized, but not universal, phenomenon found in cell lines derived from a variety of human tissues. These rapid and specific suramin-induced alterations represent a novel finding for a non-polypeptide pharmaceutical agent and question the hypothesis that suramin exerts its antitumor action simply by abrogation of growth factor action.

Positron emission tomography with 18F-dopa: interpretation and biological correlates in nonhuman primates.

Positron emission tomography (PET) was carried out, with 18F-DOPA as a ligand, in normal control monkeys and "parkinsonian" monkeys who had been treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. The following approaches were used in data analysis: ratio of 18F accumulation in specific to nonspecific brain areas and 18F-DOPA influx constant obtained using either the actual plasma 18F-DOPA or the 18F activity in a nonspecific brain area as the input function. The results from these analyses were compared to one another and to biological parameters relevant to dopaminergic function. The striatum/cortex ratio and the rate constant calculated from plasma 18F-DOPA appeared to be the most sensitive analytic techniques.

Comparison of src-family cDNAs reveals distinct mechanisms underlying focus formation in transfected fibroblasts.

Despite the intensive study of both cellular transformation and src-family protein-tyrosine kinases, there have been no direct comparisons of transforming potency for normal members of this gene-family. In this study, the focus-forming activity of normal c-src, fyn, and lck cDNAs were compared in NIH 3T3 cell transfection assays. Focus formation was studied quantitatively, and individual foci were analyzed for phosphotyrosine content and expression of appropriate translational products. Each foci arising from c-src transfectants had a marked increase in phosphotyrosine content, and the majority of these foci expressed a c-src protein with an aberrant carboxyl terminus. Foci derived from lck transfectants also had a marked increase in phosphotyrosine content, and some foci expressed a lck protein with an aberrant carboxyl terminus. In contrast, foci from fyn-transfected cells were not distinguished from G418-selected mass cultures in terms of total phosphotyrosine content or expression of p59fyn. These studies support the previously published concept that overexpression of the normal fyn protein contributes to focus formation in transfected NIH 3T3 cells but suggest that the focus-forming activity observed after c-src or lck transfections is frequently attributable to mutational events. Because lck mutations have not been previously described in transformed foci, we characterized the lck transcript expressed in two foci and identified a novel point mutation that encodes a lck protein with increased in vivo kinase and focus-forming activity.

Delayed L-phenylalanine infusion allows for simultaneous kinetic analysis and improved evaluation of specific-to-nonspecific fluorine-18-dopa uptake in brain.

The accumulation of 3-O-methyl-6-[18F]fluoro-L-DOPA (18F-30M-DOPA) in the brain from the circulation is responsible for most of the nonspecific background during 18F-DOPA positron emission tomography scanning. To increase the sensitivity of 18F-DOPA for imaging presynaptic dopamine systems, we took advantage of 18F-30M-DOPA's rapid clearance from the brain (T1/2 approximately 15-20 min). The infusion of the unlabeled amino acid L-phenylalanine, starting 75 min after 18F-DOPA administration, prevents 18F-30M-DOPA entrance into the brain through competition at the large amino acid transport system of the blood brain barrier. This method produces high specific-to-nonspecific contrast images of 18F accumulation beginning 15-30 min after onset of amino acid infusion and better sensitivity to small changes in 18F-DOPA uptake while still allowing for kinetic analysis of the data in the early time points. Kinetic and anatomical data were found to be strongly correlated.

Distribution and kinetics of 3-O-methyl-6-[18F]fluoro-L-dopa in the rhesus monkey brain.

Most attempts to model accurately [18F]-DOPA imaging of the dopamine system are based on the assumptions that its main peripheral metabolite, 3-O-methyl-6-[18F]fluoro-L-DOPA ([18F]3-OM-DOPA), crosses the blood-brain barrier but is present as a homogenous distribution throughout the brain, in part because it is not converted into [18F]DOPA in significant quantities. These assumptions were based mainly on data in rodents. Little information is available in the primate. To verify the accuracy of the above assumptions, we administered 18F-labeled 3-OM-DOPA to normal rhesus monkeys and animals with lesions of the DA nigrostriatal system. No selective 18F regional accumulation in brain was apparent in normal or lesioned animals. The plasma metabolite analysis revealed that only the negatively charged metabolites (e.g., sulfated conjugates) that do not cross the blood-brain barrier were found in significant quantities in the plasma. A one-compartment, three-parameter model was adequate to describe the kinetics of [18F]3-OM-DOPA. In conclusion, assumptions concerning [18F]3-OM-DOPA's behavior in brain appear acceptable for [18F]DOPA modeling purposes.